ABSTRACT More than half of the elderly population suffers from shoulder dysfunction and pain caused by rotator cuff injury, typically a tear of one or more of the rotator cuff tendons. Surgical repair of the rotator cuff is one of the most common orthopedic surgical procedures, with over 250,000 repairs performed each year in the United States. The goal of surgical repair is to create a strong and tough attachment between the ruptured tendon and bone in order to recover shoulder function. Unfortunately, the healthy attachment system is not recreated with current suture-based surgical techniques and is not regenerated during healing, leading to high failure rates post-operatively. These failures are primarily due to the repair techniques used to secure tendon to bone; instead of distributing muscle loads across a wide attachment footprint area, as in the healthy attachment, surgical repairs concentrate stress on a small number of suture anchor points. These stress concentrations lead to pullout of the suture from the tendon, motivating the development of technologies that distribute stresses away from suture anchors and across the attachment footprint. Motivated by this clinical problem, we implemented models and proof-of-concept experiments demonstrating that mechanically-optimized adhesive films can better distribute loads across the interface between tendon and bone and dramatically increase the load tolerance of a tendon-to-bone repair. In the current project, we advance this prior theoretical and proof-of- concept work to develop a biologically relevant adhesive for enhanced rotator cuff repair. The overall objective is to improve tendon-to-bone surgical repair outcomes through adhesive biomaterial approaches. We will take a bioinspired approach to achieve this goal: adhesives will be modeled after marine organism adhesion biochemistry. Specifically, mussel-inspired catechol-derived adhesives will be tested using in vitro and in vivo models. We hypothesize that catechol-derived adhesives will increase the initial repair strength and toughness and allow for improved tendon-to-bone healing. This will be tested across two aims: Aim 1: Develop mussel- inspired catechol-derived adhesives with appropriate mechanical properties for tendon-to-bone repair and evaluate their biocompatibility in vitro. Aim 2: Determine the efficacy of the mussel-inspired catechol-derived adhesive for improved tendon-to-bone healing in vivo. In the long term, the interposed adhesive could be modified to carry bioactive factors and/or stem cells. In addition to the mechanical augmentation to be studied in the current proposal, these factors may further enhance the long-term healing potential of the tendon-to- bone attachment.